Chronic Immune

ThrombocytoPenia By: KOK Sakada

Date: 28/07/22
Content:
1. Introduction
2. Classification & Criteria for assessment
3. Pathophysiology
4. Approach to Chronic ITP
5. Therapeutic
6. Prognostic
7. Case Report & Case Study

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I. Introduction
 Immune Thrombocytopenia in childhood is defined by
 Isolated thrombocytopenia Platelet count < 100.000/microl.
 Diagnosis of Exclusive.
 Caused by antiplatelet antibodies leading to destruction of platelets and
inhibition of production of platelets.
 One of the most common symptomatic thrombocytopenia in Children.
 Peak age: 2 to 5 years (1 to 6.4 cases per 100.000 children).
 Boy=Girl
 60%-80% self limiting, while Chronic ITP occurs in 20%.

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II. Classification & Criteria:
 Primary ITP: absence of other causes that maybe associated with
thrombocytopenia. (Unknown Cause)
 Secondary ITP: refers to immune-mediated thrombocytopenia with an
underlying causes. (ex: drug-induced, SLE, infection HIV…etc)
 Diagnostic Primary ITP:
 Newly Diagnosis ITP: < 3 months of diagnosis.
 Persistent ITP: 3  12 months, include:
 Patient not reaching spontaneous remission*.
 Patient not maintaining complete response of therapy.
 Chronic ITP: > 12 months. (continue to have thrombocytopenia from diagnosis).

*Remission: Platelet count >100 × 109/L at 12 months without treatment.

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II. Classification & Criteria
 Criteria for clinical assessment:
 Asymptomatic
 Cutaneous manifestation
 Cutaneous-mucosal manifestation
 Active bleeding:
 Epistaxis requiring nasal packing
 Gross hematuria
 Gross gastrointestinal bleeding
 Menorrhagia
 Severe gum bleeding
 Any bleeding likely to require a red blood cell transfusion or to cause severe organ damage.

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II. Classification
 Risk factor for bleeding:
 Previous head trauma or polytrauma
 Previous surgery (In the last 10 days)
 Antiplatelet therapy up to 7-10 days priors, anticoagulant therapy.
 Bleeding diathesis: Coagulopathy, vasculitis.

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II. Classification & Criteria
 Criteria for assessing response to treatment:
Complete • Plt > 100.000/uL
Response • > 6 weeks after stop from treatment.

• Plt: 30.000 - 100.000/uL

Partial Response
• > 6 weeks after stop from treatment.

No Response • No changes in clinical or biological features.

Transient • Initial improvement (clinical or biological)

response • new symptoms or a Plt < 30.000/μL in the first 6 weeks after stop from treatment. 

• Plt < 30.000/μL

Relapse
• > 6 weeks after stop from treatment following a complete or partial response. 
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III. Pathophysiology
 Presence of Anti-platelets Antibody(IgG)
 Binds to platelet membrane (GP IIb/IIIa, GP Ib/IX)
 Phagocytosis in Spleen.

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 III. Pathophysiology
1. Disturbance of the platelet
life, and release of TPO.
2. Macrophages (MF, green),
B cells, CD8*(Cytotoxic T
cells), platelet-reactive
plasma cells (PC, light blue)
3. In peripheral blood, plasma
cells and cytotoxic Tc .
4. Inhibit platelet production
by targeting MKs.

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 IV. Approach to Chronic ITP
Plt > 30.000/ul Observation
Chronic No Observation
ITP Active
Plt < 30.000/ul bleeding / Rituximax
Risk Factors Thrombopoietin
YES Immunosupressant
analogues Splenectomy

According to ASH & Spanish guideline Chronic ITP in children:

 Thrombepoetin receptors agonist( TPO-RA-Eltrompobag) rather than Rituximab and

Splenectomy

 The splenectomy is universally the last options for treatment in ITP at children.
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V. Therapeutic
 Thrombopoietin receptor agonists
 Immunosuppressants (Mycophenolate mofetil)
 Anti-CD20 monoclonal antibody (Rituximab)
 Vinca alkaloids (Vincristine)
 Splenectomy

- Bleeding severity
- Bleeding risk
Decision of treatment should be based on - Side effect of medications
- Patients preference &
Cost

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V. Therapeutic
TPO receptor agonists
Mechanisms of Action Increase in platelet production from megakaryocytes

Drug/Molecule Eltrombopag / Romiplostim

- Proven effective by increasing platelet counts in

Response approximately 80% of patients with primary ITP refractory to
other treatments.
- Long term remission after transient use: 15% of cases.
- Mostly mild symptoms, headache, URTI.
Side Effect - Eltrombopag: transaminase and bilirubin elevation
- Thrombosis events: 6%

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V. Therapeutic
Anti-CD20 monoclonal antibody
- Decrease in short-lived plasma cells by reducing their B cell
Mechanisms of Action precursors, thus decreasing antiplatelet antibodies.
- Restoration of T cell tolerance.

Drug/Molecule Rituximab

Response 30% to 60% depending on the duration of follow up

Side Effect - 1st infusion: acute reaction ( glucocorticoid administration)

- Severe infection

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V. Therapeutic
Immunosuppressants
Mechanisms of Action Inhibition of T and B cells

Drug/Molecule Azathioprine (Imurel) / Mycophenolate mofetil (MMF)

Response (MMF) reach up to 50-60% ( in 4 to 6 weeks).

Side Effect headache and gastrointestinal disturbances, mostly well

tolerated.

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V. Therapeutic
Vinca alkaloids
Inhibit macrophage function and thus reduce platelet
Mechanisms of Action
phagocytosis.

Drug/Molecule Vincristin / Vinblastin

Dosage - Vincristin: 1.5 mg/m2 per dose weekly

- Vinblastin: 6 mg/m2 per day

Response rapid responses at 7 days

- Vincristine neuropathy, alopecia, hypertension,

Side Effect hyperglycemia
- Infusion site vesication , redness, infection.

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V. Therapeutic
Splenectomy
- Decrease in peripheral platelet destruction by splenic
Target macrophages
- Removal of the site of maintenance of the autoimmune
response
- Consider in patients aged more than 5 years who are
symptomatic
Indication Non-responsive to previous therapy
-
- Severe case of chronic ITP ( life-threatening bleeding )

Response High rates of response (66%)

Complication Venous thromboembolism, post-splenectomy sepsis

- Pre-vaccination (pneumococcus, meningococcus and Hib )

Pre/Post Splenectomy Post antibiotic
-
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V. Therapeutic
 Adjunctive therapies:
 Mouth and nose bleeding:
 Antifibrinolytic agents (Tranexamic Acid)
 Intranasal DDAVP (desmopressin)
 keeping the nasal mucosa moist with a humidifier or saline nose spray)

 Heavy menses:
 Antifibrinolytic agents
 Progesterone-based treatment (medroxyprogesterone acetate)

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VI. Prognostic:
 Spontaneous remission occurs in up to 50 percent of children after months or even
years of chronic ITP.

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Case Report
A 2-year-old boy who presented to OPD on 11/07/22 with
 Skin abscess 3 days of the left hand (IV injected site), with a 2cm axillary
lymph node.
 Sudden onset of fever 1 day
 Alerted, No headache, vomit and blurry vision
 No pallor, no organomegaly in abdomen, no active bleeding
 Cushingoid appearance, with ecchymosis presented on his shin.
 Previous history revealed that he was a follow-up patient with diagnosis of
Chronic ITP treated with a Schedule Vincristine & Dexamethasone as a
combination therapy since 06/06/22.
 Investigation: CBC, CRP, Hemoculture, Urine culture and Pus swap.
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Case Report

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Case Report
Laboratory investigation:
Complete Blood Count 11/07/22
WBC 16.8 CRP 71.16

RBC 4.68 Urine Culture No growth

Hemoglobine 11.8 Blood Culture No growth

Hematocrite 34 Pus swab Gram+ cocci

(Strep, beta-haemolytic
Group A) sensitive: PNC
MCV 73

Platelet 52

Neutrophile 82% 13.78

Lymphocyte 14% 2.35

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Case Report
 Treatment
 D 5% 1/2S 500ml (7gtt/min) PIV
 Schedule Vincristine (0.05mg/kg) 11/07/22 (postpone to 13/07/22)
 Schedule Dexamethasone (40mg/m2) 18/07/22
 Cloxacilline 1g (200mg x 3)IVL  Penicilline (250mg x 3) PO
 Paracetamol 120mg/5ml (7ml x 4) PO
 Imurel (50mg) 0.5cp x 1 (PO)
 Omeprazole (20mg) 0.5cp x 1 (PO)
 Nexi 500mg 0.5cp x 3 (PO)
 Wound cleaning with betadine

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Case Report
 Treatment:
1. Vincristine (0.05mg/kg):0.6mg
 06/06 √
 13/06 √
 20/06 √
 27/06 √
 04/07 √
 11/07 postpone to 13/07
2. Dexamethasone (40mg/m2): 21mg
 06/07/08/09 June √
 20/21/22/23 June √
 04/05/06/07 July √
 18/19/20/21 July
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Case Report
 Evolution
 GA Stable
 Consciousness: Alert
 Appetite Normal
 Wound healing/clean
 No Fever/No vomit
 No active bleeding, develop generalized
petechia on Day 5
 L/S clear
 HMD stable
 Abdomen soft, No hepato-splenomegaly
 Stool pass
 Urine pass
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Case Report
11/07/22 14/07/22 18/07/22 21/07/22

WBC 16.8 6 4.5 5

RBC 4.68 4.52 4.48 4.74

Hb 11.8 10.5 11.3 11.7

Hct 34 31 31 34

MCV 73 68 70 71

Platelet 52 10 28 50

Neutrophil 82% 13.78 56% 3.36 34% 1.53 10% 0.5

Lymphocyte 14% 2.35 24% 1.44 42% 1.89 80% 4.0

CRP 71.16 1.2 - -

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Case Report
Medical History:
At first, he was a well 7-month old child, had an insidious onset of mild red spot
on his trunk without any signs of active bleeding or organomegaly. His grandma
was concerned then took him to Kanthabopha hospital, diagnosis as ITP, with
platelet count only 74.000 x106/L, treated with Prednisone almost a year
without improvement. On 27/09/21, his grandma decided to come to NPH.
The patient presented with petechia and ecchymoses on his foot, without
bleeding sign or hepatosplenomegaly. The blood test revealed:
 Isolated thrombocytopenia ( 21.000x106/L), normal formed platelet.
 Blood Group: AB RhD(+)
 Normal Coagulation test. (PT & PTT: N)
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Clinical course
27/09/21 01/10/21 03/11/21 24/12/21 24/01/22 01/02/22 03/05/22 03/06/22
Presenting Petechia Ecchymosis Ecchymosis Ecchymosis Ecchymosis Ecchymosis Ecchymosis Ecchymosis
Complaint Ecchymosis Petachia

Platelet 21 52 34 120 14 92 36 13
count
Treatments MethyPred Pred 5mg Pred 5mg Pred 5mg Pred 5mg Pred 5mg Pred 5mg Pred 5mg
given solone Imurel Imurel Imurel Imurel Imurel Imurel
50mg 50mg 50mg 50mg 50mg 50mg

Adjunctive Omeprazole (20mg)

drug

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Clinical course: 06/06/22 Schedule: Vincristine (0.05mg/kg) + Dexa
(40mg/m2)

11/06/22 20/06/22 23/06/22 26/06/22 11/07/22 14/07/22 18/07/22 21/07/22

Presenting Ecchymosis Ecchymosis Ecchymosis Ecchymosis Ecchymosis Ecchymosis Ecchymosis
Complaint Ecchymosis Diarhea + Skin abcess Skin abcess
Pechechia +
Platelet 52 18 68 186 52 10 28 50
count
Adjunctive Imurel Imurel Imurel Imurel Imurel Imurel Imurel Imurel
drug Omeprazol Ceftri Ceftri Ceftri Cloxacillin Penicillin Penicillin Penicillin
Buscopan Buscopan Buscopan Para Para Para Para
Bioflor Bioflor Bioflor Soin Soin Soin Soin
Vomena Vomena Vomena betadine betadine betadine betadine
Chlorpheni Chlorpheni Chlorpheni Omeprazol Omeprazol Omeprazol Omeprazol
Fer+folic Fer+folic Fer+folic Nexi Nexi Nexi Nexi
Omeprazol Omeprazol Omeprazol

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Study Report:

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Study Report:
Author/Year of Study Report Intervention Results Conclusion
publication Before/after treatment

Abdulah Banihashem, - 10 cases of chronic - Dexa 40 mg/m2/day Before: Plt < 30.000 - High dose
Farhad Heydarian*, ITP aged 2 to 14 in divided doses, for 4 mm3 (mean platelet dexamethasone for
MD, Pediatrician; years. days a week, then count was 29300 a few days and
Simin Hyradfar, MD, - With no response every 4 weeks for 4 ranging 4000-66000). repeated at regular
Pathologist; Morteza IVIG, oral cycles. After: Plt ↑ > 30.000 intervals is fairly
Jafarzadeh, MD, glucocorticoids, successful (Plt >
Pediatrician. Iran Rhogam and/or 30.000).
Dec 2008; Vol 18 ( o 4) splenectomy. - Fewer side effect
- With most common - Remained symptom
symptom epistasis. free at least 4
months

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References:
 https://www.uptodate.com/contents/immune-thrombocytopenia-itp-in-children-management-of-chron
ic-disease
.
 https://calgaryguide.ucalgary.ca/immune-thrombocytopenic-purpura-itp/.
 SPANISH ASSOCIATION OF PAEDIATRICS (Protocol for the study and treatment of primary immune
thrombocytopenia: ITP-2018)
 American Society of Hematology 2019 guidelines for immune thrombocytopenia.
 Bani Hashem A.A., Heydarian Farhad*, Hiradfar S., Jafarzadeh Morteza. Chronic Childhood ITP: High
Dose Parenteral Dexamethasone Therapy IRANIAN JOURNAL OF PEDIATRICS   
DECEMBER 2008 , Volume 18 , Number 4; Page(s) 381 To 382.
 Immune thrombocytopenia purpura By Prof CHEAN Sophal. 2021

Thank you.
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